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SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage

(2014) BLOOD. 123(7). p.1021-1031
Author
Organization
Abstract
SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase and a nuclease that restricts HIV-1 in noncycling cells. Germ-line mutations in SAMHD1 have been described in patients with Aicardi-Goutieres syndrome (AGS), a congenital autoimmune disease. In a previous longitudinal whole genome sequencing study of chronic lymphocytic leukemia (CLL), we revealed a SAMHD1 mutation as a potential founding event. Here, we describe an AGS patient carrying a pathogenic germ-line SAMHD1 mutation who developed CLL at 24 years of age. Using clinical trial samples, we show that acquired SAMHD1 mutations are associated with high variant allele frequency and reduced SAMHD1 expression and occur in 11% of relapsed/refractory CLL patients. We provide evidence that SAMHD1 regulates cell proliferation and survival and engages in specific protein interactions in response to DNA damage. We propose that SAMHD1 may have a function in DNA repair and that the presence of SAMHD1 mutations in CLL promotes leukemia development.
Keywords
AICARDI-GOUTIERES SYNDROME, RESTRICTION FACTOR SAMHD1, CD4(+) T-CELLS, HIV-1 RESTRICTION, MUTATIONS, CANCER, PROTEIN, VPX, TRIPHOSPHOHYDROLASE, PHOSPHORYLATION

Citation

Please use this url to cite or link to this publication:

MLA
Clifford, Ruth et al. “SAMHD1 Is Mutated Recurrently in Chronic Lymphocytic Leukemia and Is Involved in Response to DNA Damage.” BLOOD 123.7 (2014): 1021–1031. Print.
APA
Clifford, R., Louis, T., Robbe, P., Ackroyd, S., Burns, A., Timbs, A. T., Wright Colopy, G., et al. (2014). SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage. BLOOD, 123(7), 1021–1031.
Chicago author-date
Clifford, Ruth, Tania Louis, Pauline Robbe, Sam Ackroyd, Adam Burns, Adele T Timbs, Glen Wright Colopy, et al. 2014. “SAMHD1 Is Mutated Recurrently in Chronic Lymphocytic Leukemia and Is Involved in Response to DNA Damage.” Blood 123 (7): 1021–1031.
Chicago author-date (all authors)
Clifford, Ruth, Tania Louis, Pauline Robbe, Sam Ackroyd, Adam Burns, Adele T Timbs, Glen Wright Colopy, Helene Dreau, François Sigaux, Jean Gabriel Judde, Margalida Rotger, Amalio Telenti, Yea-Lih Lin, Philippe Pasero, Jonathan Maelfait, Michalis Titsias, Dena R Cohen, Shirley J Henderson, Mark T Ross, David Bentley, Peter Hillmen, Andrew Pettitt, Jan Rehwinkel, Samantha JL Knight, Jenny C Taylor, Yanick J Crow, Monsef Benkirane, and Anna Schuh. 2014. “SAMHD1 Is Mutated Recurrently in Chronic Lymphocytic Leukemia and Is Involved in Response to DNA Damage.” Blood 123 (7): 1021–1031.
Vancouver
1.
Clifford R, Louis T, Robbe P, Ackroyd S, Burns A, Timbs AT, et al. SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage. BLOOD. 2014;123(7):1021–31.
IEEE
[1]
R. Clifford et al., “SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage,” BLOOD, vol. 123, no. 7, pp. 1021–1031, 2014.
@article{8591845,
  abstract     = {SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase and a nuclease that restricts HIV-1 in noncycling cells. Germ-line mutations in SAMHD1 have been described in patients with Aicardi-Goutieres syndrome (AGS), a congenital autoimmune disease. In a previous longitudinal whole genome sequencing study of chronic lymphocytic leukemia (CLL), we revealed a SAMHD1 mutation as a potential founding event. Here, we describe an AGS patient carrying a pathogenic germ-line SAMHD1 mutation who developed CLL at 24 years of age. Using clinical trial samples, we show that acquired SAMHD1 mutations are associated with high variant allele frequency and reduced SAMHD1 expression and occur in 11% of relapsed/refractory CLL patients. We provide evidence that SAMHD1 regulates cell proliferation and survival and engages in specific protein interactions in response to DNA damage. We propose that SAMHD1 may have a function in DNA repair and that the presence of SAMHD1 mutations in CLL promotes leukemia development.},
  author       = {Clifford, Ruth and Louis, Tania and Robbe, Pauline and Ackroyd, Sam and Burns, Adam and Timbs, Adele T and Wright Colopy, Glen and Dreau, Helene and Sigaux, François and Judde, Jean Gabriel and Rotger, Margalida and Telenti, Amalio and Lin, Yea-Lih and Pasero, Philippe and Maelfait, Jonathan and Titsias, Michalis and Cohen, Dena R and Henderson, Shirley J and Ross, Mark T and Bentley, David and Hillmen, Peter and Pettitt, Andrew and Rehwinkel, Jan and Knight, Samantha JL and Taylor, Jenny C and Crow, Yanick J and Benkirane, Monsef and Schuh, Anna},
  issn         = {0006-4971},
  journal      = {BLOOD},
  keywords     = {AICARDI-GOUTIERES SYNDROME,RESTRICTION FACTOR SAMHD1,CD4(+) T-CELLS,HIV-1 RESTRICTION,MUTATIONS,CANCER,PROTEIN,VPX,TRIPHOSPHOHYDROLASE,PHOSPHORYLATION},
  language     = {eng},
  number       = {7},
  pages        = {1021--1031},
  title        = {SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage},
  url          = {http://dx.doi.org/10.1182/blood-2013-04-490847},
  volume       = {123},
  year         = {2014},
}

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